Resistance of irradiated mice to proliferation of parental or allogeneic hemopoietic cells is regulated by multiple H-2 linked genes. These hemopoietic histocompatibility (Hh) genes are phenotypically expressed only in blood-forming and leukemic cells, are not condominantly inherited, and their products are capable of stimulating host vs. graft reactions which are radioresistant in vivo. The objective of this study was to determine if cell mediated cytotoxicity (CMC) could be generated in vitro in F1 lymphocytes against parental cells, and if so, to establish if the response involve reactivity against Hh determinants. (B10xB10.A)F1 spleen cells were sensitized in culture against B10 and B10.A parental spleen cells. The effector cells were assayed on Cr51-labelled tumor target cells expressing H-2a and H-2b alleles.